The mission of the Program Development Research Group (PDRG) is to carry out a program of basic and applied research supportive of and complementary to the new drug discovery research and development programs of the National Cancer Institute. To this end, PDRG investigators have made substantial progress in a number of interrelated areas, in cellular pharmacology, ultrastructure, immunochemistry, tissue culture, and tumor cell biology, and natural products chemistry. Highlighted in this year's report are studies aimed at the further refinement of the screening models and assay methodologies used in the NCI's high-flux, in vitro antitumor and anti-HIV primary drug screens. Also described are model-development and applications efforts aimed at the detailed, follow-up evaluation of new lead compounds identified in the screens. Detailed biochemical characterizations of human tumor cell lines have included prostanoid biosynthesis, metabolic activation of 4-ipomeanol and molecular genetic approaches to the elucidation of the human lung cytochrome P450 hemoprotein monooxygenase system. New methodology has been defined for the establishment and propagation of certain "normal" (nontumor) lines in vitro. Extensive efforts have been made to develop an in vivo microencapsulation model for anti-HIV drug evaluations; however, results to date indicate this approach will not likely be feasible. Detailed studies of new lead prototype antitumor and anti-HIV compounds, both of synthetic and natural origin, have been underway; however, a more detailed report of these efforts is being deferred until the 1991 Annual Report (i.e., pending declassification of discreet structures).